Secretion of serum amyloid protein and assembly of serum amyloid protein-rich high density lipoprotein in primary mouse hepatocyte culture.
The serum amyloid protein (apo-SAA) is a unique high density lipoprotein apoprotein exhibiting dramatic increases in plasma concentration following host injury. The events involved in the secretion of apo-SAA and assembly of apo-SAA-rich lipoprotein particles were studied in primary, serum-free culture of adult BALB/c mouse hepatocytes harvested 3 h following administration of the potent apo-SAA inducer, bacterial endotoxin (50 micrograms of intraperitoneally administered Salmonella typhosa lipopolysaccharide). An approximately 3.5-fold increase in the initial rate of apo-SAA secretion was observed over that of hepatocytes isolated from control mice, whereas the rate of apo-A-I secretion was unchanged by endotoxin administration. Sodium dodecyl sulfate-gel electrophoresis and autoradiography of [35S]methionine-labeled cell products indicated the synthesis of both major mouse apo-SAA isotypes by hepatocytes. Essentially all of the secreted apo-SAA chromatographed in Sephadex G-150 with an elution volume corresponding to a molecular weight of approximately 12,000. Approximately 90% of the secreted apo-SAA was recovered in fractions (d greater than 1.21 g/ml) following ultracentrifugal fractionation. In media supplemented with human lipoproteins (100 micrograms/ml), approximately 50% of the secreted apo-SAA was recovered in the high density lipoprotein fraction. These results suggest that mouse apo-SAA is secreted in monomeric form and becomes associated with lipoproteins in the intravascular compartment.
D000682:Amyloid / Q000378:metabolism*; D000818:Animals; D016632:Apolipoprotein A-I; D001053:Apolipoproteins / Q000378:metabolism; D002478:Cells, Cultured; D004731:Endotoxins / Q000494:pharmacology; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008970:Molecular Weight; D012485:Salmonella typhi / Q000276:immunology; D000685:Serum Amyloid A Protein / Q000378:metabolism*
D000682:Amyloid; D016632:Apolipoprotein A-I; D001053:Apolipoproteins; D004731:Endotoxins; D008070:Lipopolysaccharides; D008075:Lipoproteins, HDL; D000685:Serum Amyloid A Protein; C035165:apolipoprotein SAA